AIM: To evaluate the repeatability and accuracy of iCare IC100 tonometer in measuring intraocular pressure(IOP)by comparing the correlation and difference with Goldmann applanation tonometry(GAT)and non-contact tonometer(NCT), and to compare the correlation of the three types of IOP measurement with the central corneal thickness(CCT).METHODS: Prospective study. A total of 90 outpatients(90 eyes)in Liaoning Aier Eye Hospital from March 2019 to May 2019 were randomly selected as study subjects. All patients were measured IOP using iCare IC100, NCT, and GAT. The interclass correlation coefficient(ICC)was used to evaluate the repeatability of IOP measured 3 times consecutively using an intraocular tonometer. The correlation and consistency of iCare IC100, GAT and NCT were compared by one-way ANOVA, Pearson linear correlation analysis and Bland-Altman analysis. The linear regression analysis was used to analyze the correlation of the three tonometers with CCT.RESULTS: The mean IOP measured with iCare IC100, GAT and NCT was 19.74±6.90, 19.88±7.07 and 18.47±6.31 mmHg, respectively(F=1.180, P=0.309). The measurements of iCare IC100 with GAT, iCare IC100 with NCT and GAT with NCT were all positively correlated(r=0.930, 0.946, 0.918, all P<0.05), the Bland-Altman analysis showed that the mean differences between iCare IC100 and GAT, iCare IC100 and NCT, GAT and NCT were -0.142±2.61, 1.27±2.24, and 1.41±2.81 mmHg, respectively, with 97%(87/90), 96%(86/90), and 97%(87/90)IOP differences distributed within their 95% confidence intervals. The IOP measured with iCare IC100 and CCT, GAT and CCT and NCT and CCT were all positively correlated(r=0.426, 0.353, 0.451, all P<0.01). The linear regression equations between iCare IC100, GAT and NCT measurement and CCT were iCare IC100 IOP=-19.62+0.074×CCT; GAT IOP=-13.54+0.063×CCT; NCT IOP=-19.65+0.072×CCT; that is, for every 10 μm increase in CCT, iCare IC100 measurement increased by 0.74 mmHg, GAT measurement increased by 0.63 mmHg, and NCT measurement increased by 0.72 mmHg.CONCLUSION: The iCare IC100 tonometer has good repeatability and accuracy in measuring IOP, and the CCT has a greater impact on the measurement of iCare IC100 than the GAT and NCT.

AIM: To evaluate the repeatability and accuracy of iCare IC100 tonometer in measuring intraocular pressure(IOP)by comparing the correlation and difference with Goldmann applanation tonometry(GAT)and non-contact tonometer(NCT), and to compare the correlation of the three types of IOP measurement with the central corneal thickness(CCT).METHODS: Prospective study. A total of 90 outpatients(90 eyes)in Liaoning Aier Eye Hospital from March 2019 to May 2019 were randomly selected as study subjects. All patients were measured IOP using iCare IC100, NCT, and GAT. The interclass correlation coefficient(ICC)was used to evaluate the repeatability of IOP measured 3 times consecutively using an intraocular tonometer. The correlation and consistency of iCare IC100, GAT and NCT were compared by one-way ANOVA, Pearson linear correlation analysis and Bland-Altman analysis. The linear regression analysis was used to analyze the correlation of the three tonometers with CCT.RESULTS: The mean IOP measured with iCare IC100, GAT and NCT was 19.74±6.90, 19.88±7.07 and 18.47±6.31 mmHg, respectively(F=1.180, P=0.309). The measurements of iCare IC100 with GAT, iCare IC100 with NCT and GAT with NCT were all positively correlated(r=0.930, 0.946, 0.918, all P<0.05), the Bland-Altman analysis showed that the mean differences between iCare IC100 and GAT, iCare IC100 and NCT, GAT and NCT were -0.142±2.61, 1.27±2.24, and 1.41±2.81 mmHg, respectively, with 97%(87/90), 96%(86/90), and 97%(87/90)IOP differences distributed within their 95% confidence intervals. The IOP measured with iCare IC100 and CCT, GAT and CCT and NCT and CCT were all positively correlated(r=0.426, 0.353, 0.451, all P<0.01). The linear regression equations between iCare IC100, GAT and NCT measurement and CCT were iCare IC100 IOP=-19.62+0.074×CCT; GAT IOP=-13.54+0.063×CCT; NCT IOP=-19.65+0.072×CCT; that is, for every 10 μm increase in CCT, iCare IC100 measurement increased by 0.74 mmHg, GAT measurement increased by 0.63 mmHg, and NCT measurement increased by 0.72 mmHg.CONCLUSION: The iCare IC100 tonometer has good repeatability and accuracy in measuring IOP, and the CCT has a greater impact on the measurement of iCare IC100 than the GAT and NCT.

BACKGROUND:Carboxylesterase 1 and inflammatory factors play a crucial role in regulating lipid metabolism and glucose homeostasis.However,the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats remain to be revealed. OBJECTIVE:To investigate the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats. METHODS:Thirty-two 8-week-old male Sprague-Dawley rats were randomly divided into normal control group(n=12)and modeling group(n=20)after 1 week of adaptive feeding.Rat models of type 2 diabetes mellitus were prepared by high-fat diet and single injection of streptozotocin.After successful modeling,the rats were randomly divided into diabetic control group(n=6),moderate-intensity exercise group(n=6)and high-intensity intermittent exercise group(n=6).The latter two groups were subjected to treadmill training at corresponding intensities,once a day,50 minutes each,and 5 days per week.Exercise intervention in each group was carried out for 6 weeks.After the intervention,ELISA was used to detect blood glucose and blood lipids of rats.The morphological changes of skeletal muscle were observed by hematoxylin-eosin staining.The mRNA expression levels of carboxylesterase 1 and inflammatory cytokines were detected by real-time quantitative PCR.The protein expression levels of carboxylesterase 1 and inflammatory cytokines were detected by western blot and immunofluorescence. RESULTS AND CONCLUSION:Compared with the normal control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,insulin resistance index in the diabetic control group were significantly increased(P<0.01),insulin activity was decreased(P<0.05),and the mRNA and protein levels of carboxylesterase 1,never in mitosis gene A related kinase 7(NEK7)and interleukin 18 in skeletal muscle tissue were upregulated(P<0.05).Compared with the diabetic control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,and insulin resistance index in the moderate-intensity exercise group and high-intensity intermittent exercise group were down-regulated(P<0.05),and insulin activity was increased(P<0.05).Moreover,compared with the diabetic control group,the mRNA level of NEK7 and the protein levels of carboxylesterase 1,NEK7 and interleukin 18 in skeletal muscle were decreased in the moderate-intensity exercise group(P<0.05),while the mRNA levels of carboxylesterase 1,NEK7,NOD-like receptor heat protein domain associated protein 3 and interleukin 18 and the protein levels of carboxylesterase 1 and interleukin 18 in skeletal muscle were downregulated in the high-intensity intermittent exercise group(P<0.05).Hematoxylin-eosin staining showed that compared with the diabetic control group,the cavities of myofibers in the moderate-intensity exercise group became smaller,the number of internal cavities was reduced,and the cellular structure tended to be more intact;the myocytes of rats in the high-intensity intermittent exercise group were loosely arranged,with irregular tissue shape and increased cavities in myofibers.To conclude,both moderate-intensity exercise and high-intensity intermittent exercise can reduce blood glucose,lipid,insulin resistance and carboxylesterase 1 levels in type 2 diabetic rats.Moderate-intensity exercise can significantly reduce the expression level of NEK7 protein in skeletal muscle,while high-intensity intermittent exercise can significantly reduce the expression level of interleukin 18 protein in skeletal muscle.In addition,the level of carboxylesterase 1 is closely related to the levels of NEK7 and interleukin 18.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

OBJECTIVE To assess the cost-effectiveness of durvalumab combined with chemotherapy as a first-line treatment for advanced biliary tract cancer from the perspective of the Chinese healthcare system. METHODS Using data from the TOPAZ-1 clinical trial， a three-state Markov model comprising progression-free survival （PFS）， progressive disease （PD） and death was developed， with a cycle length of 21 days and a 10-year time horizon. Patients in the observation group received durvalumab in combination with gemcitabine and cisplatin， whereas those in the control group received placebo plus the same chemotherapy regimen. The evaluation indexes were quality-adjusted life year （QALY） and the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） threshold was set at three times the 2024 Chinese per capita gross domestic product （GDP） （287 247 yuan/QALY）. The sensitivity analyses， along with scenario analyses， were performed. RESULTS In the base-case analysis， the ICER of observation group compared to control group was 1 166 344.46 yuan/QALY， far exceeding the WTP threshold， indicating that the regimen was not cost-effective. One-way sensitivity analysis identified the PD state utility， discount rate， cost of durvalumab， and PFS state utility as the main drivers of ICER variation. Probabilistic sensitivity analysis showed that， at the above WTP threshold， the probability of the acceeptance of this regimen was 0， further supporting the robustness of the base-case findings. In the scenario analysis， inclusion of a patient assistance program reduced the ICER to 235 885.16 yuan/ QALY， below the above WTP threshold， suggesting cost-effectiveness under this assistance program. However， when applying a regional WTP threshold set at three times the per capita GDP （158 475 yuan/QALY） of Gansu Province （the province with the lowest GDP in China in 2024）， the ICER remained above the threshold， indicating that the regimen was not cost-effective at the regional level. CONCLUSIONS At current pricing， durvalumab plus chemotherapy as a first-line treatment for advanced biliary tract cancer is not cost-effective in China. Although the introduction of a patient assistance program can substantially reduce the ICER and achieve cost-effectiveness at a WTP threshold set at three times the 2024 per capita GDP of China， due to limited affordability in low-income areas， the program remains not cost-effective.